Effects of concentration and vendor specific composition of formalin on postmortem MRI of the human brain

Birkl, Christoph; Soellradl, Martin; Toeglhofer, Anna M.; Krassnig, Stefanie; Leoni, Marlene; Pirpamer, Lukas; Vorauer, Thomas; Krenn, H.; Haybaeck, Johannes; Fazekas, Franz; Ropele, Stefan; Langkammer, Christian

doi:10.1002/mrm.26699

Cited by 21 publications

(30 citation statements)

References 18 publications

(42 reference statements)

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“…NMR parameters that modulate the image contrast strongly depend on the specimen preparation even if the preparations are supposedly the same. Namely, it is well known that the relaxation properties of fixed tissue depend on the tissue history, local conditions, and fixative origin and concentration . Also, we have shown that the T 2 relaxation time in fixed tissue depends on the concentration of salt and buffer in formalin fixative .…”

Section: Discussionmentioning

confidence: 51%

“…Namely, it is well known that the relaxation properties of fixed tissue depend on the tissue history, 39 local conditions, 49 and fixative origin and concentration. 40 Also, we have shown that the T 2 relaxation time in fixed tissue depends on the concentration of salt and buffer in formalin fixative. 41 Most likely there are also other parameters (e.g.…”

Section: Discussionmentioning

confidence: 88%

“…Images were recorded using RARE‐VTR (variable repetition time RARE) ( T 1 , T 2 ), MSME (multi‐slice multi‐echo) ( T 2 ), and MGE (multi‐gradient echo) ( T 2 *). Precise relaxation measurements of individual organs were not attempted, as it is known that the values depend on the fixation time, fixative origin and concentration, and concentration of salt and buffer . Therefore, only representative samples of a given specimen type (FF, FFPE, fresh, Gd doped) were used.…”

Section: Methodsmentioning

confidence: 99%

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Three‐dimensional NMR microscopy of zebrafish specimens

et al. 2018

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While zebrafish embryos in the first five days after fertilization are clear and amenable to optical analysis, older juveniles and adults are not, due to pigmentation development and tissue growth. Thus other imaging methods are needed to image adult specimens. NMR is a versatile tool for studies of biological systems and has been successfully used for in vivo zebrafish microscopy. In this work we use NMR microscopy (MRM) for assessment of zebrafish specimens, which includes imaging of formalin fixed (FF), formalin fixed and paraffin embedded (FFPE), fresh (unfixed), and FF gadolinium doped specimens. To delineate the size and shape of various organs we concentrated on 3D MRM. We have shown that at 7 T a 3D NMR image can be obtained with isotropic resolution of 50 μm/pxl within 10 min and 25 μm/pxl within 4 h. Also, we have analyzed sources of contrast and have found that in FF specimens the best contrast is obtained by T1 weighting (3D FLASH, 3D FISP), whereas in FFPE specimens T2 weighting (3D RARE) is the best. We highlight an approach to perform segmentation of the organs in order to study morphological changes associated with mutations. The broader implication of this work is development of NMR methodology for high contrast and high resolution serial imaging and automated analysis of morphology of various zebrafish mutants.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

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Three‐dimensional NMR microscopy of zebrafish specimens

et al. 2018

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“…It has previously been shown that adding 4% formaldehyde to PBS markedly shortens T 2 relaxation, and washing out bulk fixative from thin rat cortical slices (fixed for ~10 days) restores T 2 relaxation times to typical in vivo values . It has also been suggested that different brands of formalin solution might exhibit differential magnetostatic properties . Conceivably, therefore, the strong paramagnetic moments observed in some—but not all—formalin preparations might not originate from formaldehyde but from other chemical substances present in the mixture.…”

Section: Discussionmentioning

confidence: 99%

“…14 It has also been suggested that different brands of formalin solution might exhibit differential magnetostatic properties. 54 Conceivably, therefore, the strong paramagnetic moments observed in some-but not all-formalin preparations might not originate from formaldehyde but from other chemical substances present in the mixture. Our results were consistent with previous findings in that we also observed a steep reduction in R 2 * after washing out formalin with PBS which was, however, not accompanied by a corresponding QSM offset, but by a decrease in QSM variability.…”

Section: Discussionmentioning

confidence: 99%

The choice of embedding media affects image quality, tissue R₂^*, and susceptibility behaviors in post‐mortem brain MR microscopy at 7.0T

Dušek

Madai

Huelnhagen

et al. 2018

Magnetic Resonance in Med

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Purpose The quality and precision of post‐mortem MRI microscopy may vary depending on the embedding medium used. To investigate this, our study evaluated the impact of 5 widely used media on: (1) image quality, (2) contrast of high spatial resolution gradient‐echo (T1 and T2*‐weighted) MR images, (3) effective transverse relaxation rate (R2*), and (4) quantitative susceptibility measurements (QSM) of post‐mortem brain specimens. Methods Five formaldehyde‐fixed brain slices were scanned using 7.0T MRI in: (1) formaldehyde solution (formalin), (2) phosphate‐buffered saline (PBS), (3) deuterium oxide (D2O), (4) perfluoropolyether (Galden), and (5) agarose gel. SNR and contrast‐to‐noise ratii (SNR/CNR) were calculated for cortex/white matter (WM) and basal ganglia/WM regions. In addition, median R2* and QSM values were extracted from caudate nucleus, putamen, globus pallidus, WM, and cortical regions. Results PBS, Galden, and agarose returned higher SNR/CNR compared to formalin and D2O. Formalin fixation, and its use as embedding medium for scanning, increased tissue R2*. Imaging with agarose, D2O, and Galden returned lower R2* values than PBS (and formalin). No major QSM offsets were observed, although spatial variance was increased (with respect to R2* behaviors) for formalin and agarose. Conclusions Embedding media affect gradient‐echo image quality, R2*, and QSM in differing ways. In this study, PBS embedding was identified as the most stable experimental setup, although by a small margin. Agarose and Galden were preferred to formalin or D2O embedding. Formalin significantly increased R2* causing noisier data and increased QSM variance.

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A method to remove the influence of fixative concentration on postmortem T₂ maps using a kinetic tensor model

Tendler

Foxley

et al. 2021

Human Brain Mapping

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Formalin fixation has been shown to substantially reduce T 2 estimates, primarily driven by the presence of fixative in tissue. Prior to scanning, post-mortem samples are often placed into a fluid that has more favourable imaging properties. This study investigates whether there is evidence for a change in T 2 in regions close to the tissue surface due to fixative outflux into this surrounding fluid. Furthermore, we investigate whether a simulated spatial map of fixative concentration can be used as a confound regressor to reduce T 2 inhomogeneity. To achieve this, T 2 maps and diffusion tensor estimates were obtained in 14 whole, formalin-fixed post-mortem brains placed in Fluorinert approximately 48 hr prior to scanning. Seven brains were fixed with 10% formalin and seven brains were fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a proposed kinetic tensor (KT) model, which incorporates voxelwise diffusion tensor estimates to account for diffusion anisotropy and tissue-specific diffusion coefficients. Brains fixed with 10% NBF revealed a spatial T 2 pattern consistent with modelled fixative outflux. Confound regression of fixative concentration reduced T 2 inhomogeneity across both white and grey matter, with the greatest reduction attributed to the KT model versus simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin.Correlations between the transverse relaxation rate R 2 and ferritin/myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between R 2 and PLP for the two fixative types after KT correction.

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Effects of concentration and vendor specific composition of formalin on postmortem MRI of the human brain

Cited by 21 publications

References 18 publications

Three‐dimensional NMR microscopy of zebrafish specimens

Three‐dimensional NMR microscopy of zebrafish specimens

The choice of embedding media affects image quality, tissue R₂^*, and susceptibility behaviors in post‐mortem brain MR microscopy at 7.0T

A method to remove the influence of fixative concentration on postmortem T₂ maps using a kinetic tensor model

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Effects of concentration and vendor specific composition of formalin on postmortem MRI of the human brain

Cited by 21 publications

References 18 publications

Three‐dimensional NMR microscopy of zebrafish specimens

Three‐dimensional NMR microscopy of zebrafish specimens

The choice of embedding media affects image quality, tissue R2*, and susceptibility behaviors in post‐mortem brain MR microscopy at 7.0T

A method to remove the influence of fixative concentration on postmortem T2 maps using a kinetic tensor model

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The choice of embedding media affects image quality, tissue R₂^*, and susceptibility behaviors in post‐mortem brain MR microscopy at 7.0T

A method to remove the influence of fixative concentration on postmortem T₂ maps using a kinetic tensor model